JOP20210231A1 - مركبات ترابطية مستهدفة كمركبات علاجية - Google Patents

مركبات ترابطية مستهدفة كمركبات علاجية

Info

Publication number
JOP20210231A1
JOP20210231A1 JOP/2021/0231A JOP20210231A JOP20210231A1 JO P20210231 A1 JOP20210231 A1 JO P20210231A1 JO P20210231 A JOP20210231 A JO P20210231A JO P20210231 A1 JOP20210231 A1 JO P20210231A1
Authority
JO
Jordan
Prior art keywords
targeting ligands
expression
compounds
target
inhibiting oligomeric
Prior art date
Application number
JOP/2021/0231A
Other languages
English (en)
Inventor
Pei Tao
B Rozema David
H Wakefield Darren
V Blokhin Andrei
D Benson Jonathan
Li Zhen
Fleitz Fred
Original Assignee
Arrowhead Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Arrowhead Pharmaceuticals Inc filed Critical Arrowhead Pharmaceuticals Inc
Publication of JOP20210231A1 publication Critical patent/JOP20210231A1/ar

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
    • A61K48/0025—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
    • A61K48/0033—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being non-polymeric
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/317—Chemical structure of the backbone with an inverted bond, e.g. a cap structure
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3521—Methyl
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3525—MOE, methoxyethoxy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • C12N2310/3533—Halogen

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)

Abstract

يتعلق الاختراع الحالي بالكشف عن مركبات ترابطية مستهدفة جديدة يمكن ربطها بمركبات، هذة المركبات العلاجية التى تكون مفيدة في توجيه المركبات إلى داخل الجسم الحي المستهدف. يمكن أن تعمل المركبات الترابطية المستهدفة التي تم الكشف عنها في هذه الوثيقة على استهداف مركبات أوليجومرية لتثبيط التعبير، مثل عوامل ANAi، إلى خلايا الكبد لتضمين التعبير الجيني. يمكن استخدام المركبات الترابطية المستهدفة التي تم الكشف عنها في هذه الوثيقة، عند ترافقها مع مركب أوليجومرية لتثبيط التعبير في مجموعة متنوعة من التطبيقات التي تتضمن الاستخدام في تطبيقات علاجية، تشخيصية، التحقق من الهدف، وتطبيقات اكتشاف مجموعة العوامل الوراثية. تكون التركيبات التي تتضمن المركبات الترابطية المستهدفة التي تم الكشف عنها في هذه الوثيقة عند ربطها بمركبات أوليجومرية لتثبيط التعبير قادرة على التوسط فى التعبير عن متواليات حمض نووي مستهدفة في خلايا الكبد، مثل الخلايا الكبدية، التي يمكن أن تكون مفيدة في معالجة الأمراض أو الحالات التي تستجيب لتثبيط التعبير الجيني أو النشاط في خلية، نسيج أو عضو.
JOP/2021/0231A 2016-03-07 2021-08-19 مركبات ترابطية مستهدفة كمركبات علاجية JOP20210231A1 (ar)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662304652P 2016-03-07 2016-03-07
US201662370754P 2016-08-04 2016-08-04
US201662426916P 2016-11-28 2016-11-28

Publications (1)

Publication Number Publication Date
JOP20210231A1 true JOP20210231A1 (ar) 2023-01-30

Family

ID=59723428

Family Applications (2)

Application Number Title Priority Date Filing Date
JOP/2017/0057A JOP20170057B1 (ar) 2016-03-07 2017-03-07 مركبات ترابطية مستهدفة كمركبات علاجية
JOP/2021/0231A JOP20210231A1 (ar) 2016-03-07 2021-08-19 مركبات ترابطية مستهدفة كمركبات علاجية

Family Applications Before (1)

Application Number Title Priority Date Filing Date
JOP/2017/0057A JOP20170057B1 (ar) 2016-03-07 2017-03-07 مركبات ترابطية مستهدفة كمركبات علاجية

Country Status (14)

Country Link
US (3) US10246709B2 (ar)
EP (1) EP3426261A4 (ar)
JP (3) JP6983797B2 (ar)
KR (3) KR102348425B1 (ar)
CN (2) CN113797348A (ar)
AU (2) AU2017229469B2 (ar)
BR (1) BR112018068230B1 (ar)
CA (1) CA3011946A1 (ar)
IL (3) IL296377A (ar)
JO (2) JOP20170057B1 (ar)
MX (3) MX2018009854A (ar)
TW (3) TWI783434B (ar)
UY (1) UY37146A (ar)
WO (1) WO2017156012A1 (ar)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JOP20210043A1 (ar) 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc تراكيب وأساليب لتثبيط تعبير جيني للـ lpa
CN113797348A (zh) * 2016-03-07 2021-12-17 箭头药业股份有限公司 用于治疗性化合物的靶向配体
JOP20170161A1 (ar) 2016-08-04 2019-01-30 Arrowhead Pharmaceuticals Inc عوامل RNAi للعدوى بفيروس التهاب الكبد ب
JP6989521B2 (ja) 2016-09-02 2022-01-05 アローヘッド ファーマシューティカルズ インコーポレイテッド 標的化リガンド
AU2018208505B2 (en) 2017-01-10 2024-03-07 Arrowhead Pharmaceuticals, Inc. Alpha-1 antitrypsin (AAT) RNAi agents, compositions including AAT RNAi agents, and methods of use
TN2020000039A1 (en) 2017-09-11 2021-10-04 Arrowhead Pharmaceuticals Inc Rnai agents and compositions for inhibiting expression of apolipoprotein c-iii (apoc3)
SG11201912188RA (en) 2017-09-14 2020-01-30 Arrowhead Pharmaceuticals Inc Rnai agents and compositions for inhibiting expression of angiopoietin-like 3 (angptl3), and methods of use
AU2018352379A1 (en) 2017-10-17 2020-06-04 Arrowhead Pharmaceuticals, Inc. RNAi agents and compositions for inhibiting expression of Asialoglycoprotein receptor 1
AU2019342117A1 (en) * 2018-09-19 2021-03-04 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of 17beta-HSD type 13- (HSD17B13), compositions thereof, and methods of use
CN111377985B (zh) * 2018-12-29 2023-11-10 苏州瑞博生物技术股份有限公司 化合物和缀合物及其制备方法和用途
US20220305046A1 (en) 2019-06-06 2022-09-29 Arrowhead Pharmaceuticals, Inc. Methods for the treatment of alpha-1 antitrypsin deficiency (aatd)
EP3986562A1 (en) 2019-06-18 2022-04-27 Janssen Sciences Ireland Unlimited Company Combination of hepatitis b virus (hbv) vaccines and hbv-targeting rnai
CA3143047A1 (en) 2019-06-25 2020-12-30 Amgen Inc. Purification methods for carbohydrate-linked oligonucleotides
JP2023519215A (ja) 2020-03-23 2023-05-10 アムジエン・インコーポレーテツド 化学修飾核酸に対するモノクローナル抗体及びその使用
JP2023519246A (ja) 2020-03-26 2023-05-10 アローヘッド ファーマシューティカルズ インコーポレイテッド ＰＮＰＬＡ３の発現を阻害するためのＲＮＡｉ薬、その医薬組成物、及び使用方法
US20230250125A1 (en) 2020-04-01 2023-08-10 Janssen Biopharma, Inc. Nucleic acid polymers
WO2021206182A1 (ja) * 2020-04-10 2021-10-14 学校法人 聖マリアンナ医科大学 化合物、造影剤、及び化合物の製造方法
TW202214301A (zh) * 2020-06-16 2022-04-16 大陸商上海拓界生物醫藥科技有限公司 一種碳水化合物分子簇及其製備方法和醫藥用途
US20230348905A1 (en) 2020-09-15 2023-11-02 Arrowhead Pharmaceuticals, Inc. Methods for the reduction of z-aat protein levels
TW202233837A (zh) 2020-11-05 2022-09-01 美商安進公司 用靶向ＬＰＡ的ＲＮＡｉ構建體治療動脈粥樣硬化性心血管疾病之方法
US20240175020A1 (en) 2020-12-23 2024-05-30 Flagship Pioneering Innovations Vi, Llc Compositions of modified trems and uses thereof
TW202304472A (zh) 2021-04-23 2023-02-01 美商格納生物公司 經聚醣修飾之核酸、製備方法及治療用途
US11549112B1 (en) 2021-06-21 2023-01-10 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of xanthine dehydrogenase (XDH), pharmaceutical compositions thereof, and methods of use
CN117377765A (zh) * 2021-07-02 2024-01-09 上海拓界生物医药科技有限公司 一种核酸配体及其缀合物、其制备方法和用途
CN114703184B (zh) * 2022-03-11 2024-06-18 厦门甘宝利生物医药有限公司 Lpa抑制剂及其用途
WO2023196941A1 (en) 2022-04-08 2023-10-12 Arrowhead Pharmaceuticals, Inc. Treatment of a non-alcoholic fatty liver disease
TW202406926A (zh) 2022-05-02 2024-02-16 美商安進公司 用於製備碳水化合物靶向部分及其中間體之方法
WO2023233290A1 (en) 2022-05-31 2023-12-07 Janssen Sciences Ireland Unlimited Company Rnai agents targeting pd-l1
WO2023250112A1 (en) 2022-06-22 2023-12-28 Flagship Pioneering Innovations Vi, Llc Compositions of modified trems and uses thereof

Family Cites Families (97)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US4751219A (en) 1985-02-05 1988-06-14 Nederlandse Centrale Organisatie Voor Toegepast-Natuur-Wetenschappelijk Onderzoek Synthetic glycolipides, a process for the preparation thereof and several uses for these synthetic glycolipides
NL9201440A (nl) 1992-08-11 1994-03-01 Univ Leiden Triantennaire clusterglycosiden, hun bereiding en toepassing.
US6908903B1 (en) 1994-12-07 2005-06-21 Aletheon Pharmaceuticals, Inc. Cluster clearing agents
US6172045B1 (en) 1994-12-07 2001-01-09 Neorx Corporation Cluster clearing agents
US20030119724A1 (en) 1995-11-22 2003-06-26 Ts`O Paul O.P. Ligands to enhance cellular uptake of biomolecules
JP2000501414A (ja) 1995-11-22 2000-02-08 ザ・ジョンズ・ホプキンス・ユニバーシティー 生体分子の細胞取り込みを高めるリガンド
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
US6620916B1 (en) 1996-09-26 2003-09-16 Ajinomoto Co., Inc. Modified physiologically active proteins and medicinal compositions containing the same
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6811996B1 (en) * 1998-10-30 2004-11-02 Daiichi Pharmaceutical Co., Ltd. DDS compounds and method for assaying the same
US6383812B1 (en) 1999-05-28 2002-05-07 Academia Sinica Anti liver disease drug R-YEEE and method of synthesizing branched galactose-terminal glycoproteins
US8541548B2 (en) 1999-06-07 2013-09-24 Arrowhead Madison Inc. Compounds and methods for reversible modification of biologically active molecules
US20080281041A1 (en) 1999-06-07 2008-11-13 Rozema David B Reversibly Masked Polymers
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US20070026394A1 (en) 2000-02-11 2007-02-01 Lawrence Blatt Modulation of gene expression associated with inflammation proliferation and neurite outgrowth using nucleic acid based technologies
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
DK1309726T4 (en) 2000-03-30 2019-01-28 Whitehead Inst Biomedical Res RNA Sequence-Specific Mediators of RNA Interference
CZ308053B6 (cs) 2000-12-01 2019-11-27 Max Planck Gesellschaft Izolovaná molekula dvouřetězcové RNA, způsob její výroby a její použití
CN100406065C (zh) 2000-12-01 2008-07-30 细胞工厂治疗公司 糖基化/半乳糖基化肽、双官能接头和核苷酸单体/多聚体的缀合物以及相关的组合物和使用方法
ATE427948T1 (de) 2001-04-24 2009-04-15 Purdue Research Foundation Folat-mimetika und deren folatrezeptorbindende konjugate
EP1572067A4 (en) 2001-05-18 2009-05-13 Sirna Therapeutics Inc CONJUGATES AND COMPOSITIONS FOR CELL DELIVERY
US7109165B2 (en) 2001-05-18 2006-09-19 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
AU2002313699A1 (en) 2001-07-20 2003-03-03 Ribozyme Pharmacuticals, Inc. Enzymatic nucleic acid peptide conjugates
US7439043B2 (en) 2001-10-10 2008-10-21 Neose Technologies, Inc. Galactosyl nucleotide sugars
US20100240730A1 (en) 2002-02-20 2010-09-23 Merck Sharp And Dohme Corp. RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA)
EP1543019A2 (en) 2002-09-11 2005-06-22 Santaris Pharma A/S Modified pna molecules
EP3450559A1 (en) 2003-03-07 2019-03-06 Alnylam Pharmaceuticals, Inc. Therapeutic compositions
WO2004090108A2 (en) 2003-04-03 2004-10-21 Alnylam Pharmaceuticals Irna conjugates
ES2702942T3 (es) 2003-04-17 2019-03-06 Alnylam Pharmaceuticals Inc Agentes de ARNi modificados
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
WO2004101619A1 (ja) 2003-05-15 2004-11-25 Shionogi Co., Ltd. 機能的糖ペプチドの合理的設計および合成
JP5192234B2 (ja) 2004-08-10 2013-05-08 アルナイラム ファーマシューティカルズ， インコーポレイテッド 化学修飾オリゴヌクレオチド
US20090203132A1 (en) 2004-09-09 2009-08-13 Swayze Eric E Pyrrolidinyl groups for attaching conjugates to oligomeric compounds
US20060148740A1 (en) 2005-01-05 2006-07-06 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
EP1841867A1 (en) 2005-01-24 2007-10-10 Avaris AB COMPLEX CONTAINING SiRNA, ShRNA OR ANTISENSE MOLECULE AND FUNCTIONAL ENTITY, FOR IMPROVED SPECIFICITY AND DELIVERY
US8658211B2 (en) 2006-08-18 2014-02-25 Arrowhead Madison Inc. Polyconjugates for in vivo delivery of polynucleotides
JP5274461B2 (ja) 2006-08-18 2013-08-28 アローヘッド リサーチ コーポレイション ポリヌクレオチドのインビボ送達のためのポリ結合体
EP2604284A1 (en) 2007-02-16 2013-06-19 KTB Tumorforschungsgesellschaft mbH Receptor And Antigen Targeted Prodrug
US8877917B2 (en) 2007-04-23 2014-11-04 Alnylam Pharmaceuticals, Inc. Glycoconjugates of RNA interference agents
EP2231194B1 (en) 2007-12-04 2017-02-22 Alnylam Pharmaceuticals Inc. Folate-irna conjugates
CA3043911A1 (en) 2007-12-04 2009-07-02 Arbutus Biopharma Corporation Targeting lipids
EP2245039A4 (en) 2008-01-31 2012-06-06 Alnylam Pharmaceuticals Inc OPTIMIZED METHODS FOR EXPORING DSRNA TO TARGET THE PCSK9 GEN
WO2009120878A2 (en) 2008-03-26 2009-10-01 Alnylam Pharmaceuticals, Inc. Non-natural ribonucleotides, and methods of use thereof
AU2009234266B2 (en) 2008-04-11 2015-08-06 Tekmira Pharmaceuticals Corporation Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
CA2737661C (en) 2008-09-23 2019-08-20 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
EA029762B1 (ru) 2008-10-20 2018-05-31 Элнилэм Фармасьютикалз, Инк. Композиции и способы для ингибирования экспрессии транстиретина
EP2447274B1 (en) 2008-10-24 2017-10-04 Ionis Pharmaceuticals, Inc. Oligomeric compounds and methods
NO2355851T3 (ar) 2008-11-10 2018-09-01
WO2010129709A1 (en) 2009-05-05 2010-11-11 Alnylam Pharmaceuticals, Inc. Lipid compositions
KR20230098713A (ko) 2009-06-10 2023-07-04 알닐람 파마슈티칼스 인코포레이티드 향상된 지질 조성물
WO2011005980A1 (en) 2009-07-09 2011-01-13 Intradigm Corporation Novel heterobifunctional polyethylene glycol reagents, their preparation and uses thereof
TWI458493B (zh) 2009-09-25 2014-11-01 Iner Aec Executive Yuan 新穎肝標靶藥劑與合成方法
TWI388338B (zh) 2009-10-26 2013-03-11 Iner Aec Executive Yuan 對聚合醣鏈進行放射標誌以作為肝受體造影劑之方法
TWI391144B (zh) 2009-10-26 2013-04-01 Iner Aec Executive Yuan 一種定量肝殘餘功能的檢驗方法與其新穎肝受體造影檢驗藥劑
WO2011072290A2 (en) 2009-12-11 2011-06-16 The Regents Of The University Of Michigan Targeted dendrimer-drug conjugates
PT2539451E (pt) 2010-02-24 2016-03-28 Arrowhead Res Corp Composições para entrega de arnsi dirigida ao alvo
EP2553019A1 (en) 2010-03-26 2013-02-06 Mersana Therapeutics, Inc. Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof
US20130236968A1 (en) 2010-06-21 2013-09-12 Alnylam Pharmaceuticals, Inc. Multifunctional copolymers for nucleic acid delivery
US9290760B2 (en) 2010-09-15 2016-03-22 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
WO2012068187A1 (en) * 2010-11-19 2012-05-24 Merck Sharp & Dohme Corp. Poly(amide) polymers for the delivery of oligonucleotides
US8501930B2 (en) * 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system
EP3192800A1 (en) * 2010-12-17 2017-07-19 Arrowhead Pharmaceuticals, Inc. Galactose cluster-pharmacokinetic modulator targeting moiety for sirna
MX342609B (es) 2010-12-29 2016-10-06 Hoffmann La Roche Conjugados de molecula pequeña para suministro intracelular de acidos nucleicos.
RS61447B1 (sr) 2011-04-21 2021-03-31 Glaxo Group Ltd Modulacija ekspresije virusa hepatitisa b (hbv)
JP6165723B2 (ja) * 2011-06-30 2017-07-19 アローヘッド ファーマシューティカルズ インコーポレイテッド Ｂ型肝炎ウイルスの遺伝子発現を阻害するための組成物および方法
MX2014001971A (es) 2011-08-26 2014-03-31 Arrowhead Res Corp Polimeros de poli(vinilester) para suministro de acido nucleico in vivo.
US10023861B2 (en) 2011-08-29 2018-07-17 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
BR112014004528A2 (pt) * 2012-04-18 2019-09-24 Arrowhead Res Corp polímeros de poli(acrilato) para entrega de ácido nucleico in vivo
AR090906A1 (es) 2012-05-02 2014-12-17 Merck Sharp & Dohme Conjugados que contienen tetragalnac y procedimientos para la administracion de oligonucleotidos
EP3919620A1 (en) 2012-05-02 2021-12-08 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
AR090905A1 (es) 2012-05-02 2014-12-17 Merck Sharp & Dohme Conjugados que contienen tetragalnac y peptidos y procedimientos para la administracion de oligonucleotidos, composicion farmaceutica
US9150602B2 (en) * 2012-07-24 2015-10-06 Atomic Energy Council, Institute Of Nuclear Energy Research Precursor used for labeling hepatorcyte receptor and containing trisaccharide and diamide demercaptide ligand, method for preparing the same, radiotracer and pharmaceutical composition of the same
AU2013299717B2 (en) 2012-08-06 2018-06-28 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugated RNA agents and process for their preparation
KR20150083920A (ko) 2012-11-15 2015-07-20 로슈 이노베이션 센터 코펜하겐 에이/에스 항 apob 안티센스 접합체 화합물
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
KR20150110562A (ko) 2013-01-30 2015-10-02 에프. 호프만-라 로슈 아게 Ｌｎａ 올리고뉴클레오타이드 탄수화물 컨쥬게이트
SG11201508925WA (en) 2013-05-01 2015-11-27 Regulus Therapeutics Inc Microrna compounds and methods for modulating mir-122
RU2686080C2 (ru) 2013-05-01 2019-04-24 Ионис Фармасьютикалз, Инк. Композиции и способы
EP4039278A1 (en) 2013-07-11 2022-08-10 Alnylam Pharmaceuticals, Inc. Oligonucleotide-ligand conjugates and process for their preparation
EP3065758B1 (en) 2013-11-06 2019-09-25 Merck Sharp & Dohme Corp. Peptide containing conjugates for dual molecular delivery of oligonucleotides
KR102149571B1 (ko) 2014-05-01 2020-08-31 아이오니스 파마수티컬즈, 인코포레이티드 성장 호르몬 수용체 발현을 조절하기 위한 조성물 및 방법
WO2015188194A1 (en) * 2014-06-06 2015-12-10 Isis Pharmaceuticals, Inc. Compositions and methods for enhanced intestinal absorption of conjugated oligomeric compounds
TW201620526A (zh) 2014-06-17 2016-06-16 愛羅海德研究公司 用於抑制α－１抗胰蛋白酶基因表現之組合物及方法
RU2017101140A (ru) 2014-07-01 2018-08-02 Джима Тт С.П.А. Упаковка для курительных изделий
AU2015317958A1 (en) 2014-09-15 2017-05-04 Qubole, Inc. Systems and methods for providing metadata-aware background caching in data analysis
SG11201702877TA (en) 2014-10-10 2017-05-30 Hoffmann La Roche Galnac phosphoramidites, nucleic acid conjugates thereof and their use
US9803205B2 (en) * 2015-03-17 2017-10-31 Arrowhead Pharmaceuticals, Inc. Compositions and methods for inhibiting gene expression of factor XII
US20160272970A1 (en) * 2015-03-17 2016-09-22 Arrowhead Madison Inc. RNA Interference Agents
AU2016306275A1 (en) 2015-08-07 2018-02-08 Arrowhead Pharmaceuticals, Inc. RNAi therapy for Hepatitis B virus infection
JOP20210043A1 (ar) * 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc تراكيب وأساليب لتثبيط تعبير جيني للـ lpa
CN113797348A (zh) * 2016-03-07 2021-12-17 箭头药业股份有限公司 用于治疗性化合物的靶向配体
JP6989521B2 (ja) 2016-09-02 2022-01-05 アローヘッド ファーマシューティカルズ インコーポレイテッド 標的化リガンド
AU2018208505B2 (en) * 2017-01-10 2024-03-07 Arrowhead Pharmaceuticals, Inc. Alpha-1 antitrypsin (AAT) RNAi agents, compositions including AAT RNAi agents, and methods of use
CA3048661A1 (en) 2017-01-30 2018-08-02 Arrowhead Pharmaceuticals Inc. Compositions and methods for inhibition of factor xii gene expression

Also Published As

Publication number Publication date
JP6983797B2 (ja) 2021-12-17
CA3011946A1 (en) 2017-09-14
KR102515329B1 (ko) 2023-03-29
US20190211333A1 (en) 2019-07-11
CN109069529B (zh) 2021-08-20
BR112018068230A2 (pt) 2019-07-30
TWI783434B (zh) 2022-11-11
TWI727009B (zh) 2021-05-11
IL261598A (en) 2018-10-31
EP3426261A1 (en) 2019-01-16
JP2019511491A (ja) 2019-04-25
TW202203972A (zh) 2022-02-01
IL296377A (en) 2022-11-01
MX2018009854A (es) 2018-11-09
MX2023006334A (es) 2023-06-12
AU2023203102A1 (en) 2023-06-08
IL288341B (en) 2022-10-01
EP3426261A4 (en) 2020-03-25
KR102348425B1 (ko) 2022-01-10
JP2022023242A (ja) 2022-02-07
US20210189394A1 (en) 2021-06-24
IL288341A (en) 2022-01-01
KR20220005633A (ko) 2022-01-13
BR112018068230B1 (pt) 2024-02-27
IL288341B2 (en) 2023-02-01
US12116573B2 (en) 2024-10-15
MX2023006332A (es) 2023-06-12
WO2017156012A1 (en) 2017-09-14
US10246709B2 (en) 2019-04-02
AU2017229469A1 (en) 2018-08-09
AU2017229469B2 (en) 2023-02-23
JP7485642B2 (ja) 2024-05-16
KR20230048446A (ko) 2023-04-11
JOP20170057B1 (ar) 2022-03-14
CN113797348A (zh) 2021-12-17
JP2024097862A (ja) 2024-07-19
IL261598B (en) 2021-12-01
KR20180121925A (ko) 2018-11-09
CN109069529A (zh) 2018-12-21
UY37146A (es) 2017-09-29
US20170253875A1 (en) 2017-09-07
TW201735953A (zh) 2017-10-16
TWI842117B (zh) 2024-05-11
TW202330035A (zh) 2023-08-01

Similar Documents

Publication Publication Date Title
JOP20210231A1 (ar) مركبات ترابطية مستهدفة كمركبات علاجية
JOP20210207A1 (ar) مركبات ترابطية مستهدفة
WO2017053431A3 (en) Allele selective gene editing and uses thereof
CY1123693T1 (el) Παραγοντες rnai, συνθεσεις και μεθοδοι χρησης αυτων για τη θεραπευτικη αγωγη σχετιζομενων με τρανσθυρετινη (ttr) ασθενειων
MX2023008478A (es) Nucleótidos modificados con 5´-ciclo-fosfonato.
TN2020000038A1 (en) Rnai agents and compositions for inhibiting expression of angiopoietin-like 3 (angptl3), and methods of use
MX2023005397A (es) Escision de secuencias de acido nucleico retrovirales.
BR112018012894A2 (pt) materiais e métodos para tratamento de esclerose lateral amiotrófica e/ou degeneração lobular frontotemporal
EP4339288A3 (en) Oligonucleotide probes and uses thereof
NZ733747A (en) Kdm1a inhibitors for the treatment of disease
WO2016106400A3 (en) Rna interference agents for gst-pi gene modulation
MX343160B (es) Dicetopiperazinas para uso en inhibir hiperpermeabilidad vascular.
MX2016001587A (es) Inhibidores de kdm1a para el tratamiento de enfermedades.
MX2015002044A (es) Pirazolil-ureas como inhibidores de quinasa.
EA201201648A1 (ru) Стимуляторы sgc
EA201792103A1 (ru) Композиции и способы для ингибирования экспрессии генов hif2альфа
WO2008073919A3 (en) Mir-20 regulated genes and pathways as targets for therapeutic intervention
WO2013158309A3 (en) Non-disruptive gene targeting
MX2019006379A (es) Induccion de gen de trail de molecula pequeña en celulas normales y tumorales como una terapia anticancer.
BR112016029781A2 (pt) composições e métodos para inibir a expressão de gene de alfa-1 antitripsina
WO2012024396A3 (en) Compositions and methods for delivering nucleic acid molecules and treating cancer
AU2012358181A8 (en) Compositions and methods for the delivery of biologically active RNAs
WO2014111876A3 (en) Modulation of mitophagy and use thereof
EP3581653A3 (en) Methods and compositions for treating cancer using peptide nucleic acid-based agents
BR112017016883A2 (pt) compostos com atividade antitumoral